Research has involved the study of the immunologic and genetic mechanisms involved in the development and expression of autoimmune disease. Four murine models of autoimmune disease; NZB and PN mice and mice homozygous for the mutant genes 1pr or me were studied for phenotypic and functional abnormalities of T and B lymphocytes prior to and after the onset of severe disease. B cells from each autoimmune strain were hyperactive as evidenced by a decrease in the level of expression of cell surface IgM and IgD, a marked increase in the frequency of splenic plasma cells and cells spontaneously secreting immunoglobulin and the production of autoantibodies. In contrast to the other strains, 1pr/1pr mice had a high incidence of Thy 1+, Ly 1+, 2- T cells that also bore markers normally only expressed on B lymphocytes. Gene reorganization studies showed an rearrangement of immunoglobulin heavy chain genes in these cells. This abnormal T cell population was deficient in T helper cell activity and produced decreased amounts of Interleukin-2. B6 me/me mice also had unique abnormalities of T cells. These included a decrease in the frequency of all T cells in the spleen and an increase in the proportion of Ly2+ T cells in lymph node. Severe abnormalities in T lymphocyte function were in evidence as early as 4 weeks of age.